Department of Pediatrics, The Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States.
Department of Public Health Science, The Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States.
Physiol Genomics. 2024 Oct 1;56(10):691-697. doi: 10.1152/physiolgenomics.00045.2024. Epub 2024 Sep 2.
The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of , and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either or . All interactions were intergenic except one, among SNPs of . The remaining interactions were either among SNPs of hydrophilic SPs alone ( = 8) or among SNPs of both hydrophilic or hydrophobic SPs ( = 11). Our findings indicate that SNPs of all s may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of and/or SNPs in these interactions underscores their significance in RSV severity. Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of and SNPs. This highlights the comprehensive role of all SPs in genetic susceptibility to RSV severity, shedding light on potential avenues for targeted interventions.
呼吸道合胞病毒 (RSV) 的严重程度可能与宿主遗传易感性有关。表面活性蛋白 (SP) 基因的遗传变异与 RSV 的严重程度有关，但 SNP-SNP 相互作用的影响仍未得到探索。因此，我们使用一种新的统计模型来研究基因的 SNP-SNP 相互作用与 RSV 严重程度之间的关联，采用两重和三重相互作用模型。我们分析了 405 名经前瞻性诊断为 RSV 的儿童的基因型和临床数据，将其分为中度或重度 RSV 组。使用 Wang 的统计模型，我们以病例对照的方式研究了 SNP-SNP 相互作用与 RSV 严重程度之间的显著关联。我们首先观察到，在两重 SNP 模型中，三重 SNP 相互作用与严重 RSV 风险增加有关。一个基因内相互作用发生在 和 的 SNP 之间，另外两个是基因间相互作用，涉及单独的亲水和疏水 SP 的 SNP。我们还观察到，在三重 SNP 模型中，22 个 SNP-SNP 相互作用与 RSV 严重程度有关。其中，20 个是独特的，12 个和 10 个 SNP 相互作用分别与 RSV 严重程度增加或降低的风险相关，包括至少一个 或 的 SNP。所有的相互作用都是基因间的，只有一个位于 和 的 SNP 之间。其余的相互作用要么发生在亲水 SP 的 SNP 之间（=8），要么发生在亲水或疏水 SP 的 SNP 之间（=11）。我们的研究结果表明，所有 SP 的 SNP 可能导致 RSV 严重程度的遗传易感性。然而， 和/或 的 SNP 在这些相互作用中的主要参与突显了它们在 RSV 严重程度中的重要性。虽然表面活性蛋白 (SP) 基因的遗传变异与呼吸道合胞病毒 (RSV) 的严重程度有关，但 SP 基因的单核苷酸多态性 (SNP)-SNP 相互作用的影响仍未得到探索。我们使用先进的统计模型发现了 22 个与 RSV 严重程度相关的 SNP-SNP 相互作用，其中显著涉及 和 SNPs。这突出了所有 SP 在 RSV 严重程度遗传易感性中的综合作用，为有针对性的干预措施提供了潜在途径。
